Heart researchers find cell renewal using nuke link

By Nicholas Wade / NY TIMES NEWS SERVICE

In a finding that may open new approaches to treating heart disease, Swedish scientists have succeeded in measuring a highly controversial property of the human heart: the rate at which its muscle cells are renewed during a person’s lifetime.

The finding overturns what has long been conventional wisdom: that the heart cannot produce new muscle cells and so people die with the same heart they were born with.

About 1 percent of heart muscle cells are replaced every year at age 25, and that rate gradually falls to less than half a percent per year by age 75, a team of researchers led by Jonas Frisen of the Karolinska Institute in Stockholm concluded.

The upshot is that about half of the heart’s muscle cells are exchanged in the course of a normal lifetime, the Swedish group calculates. Its results were to be published on Friday in the journal Science.

“I think this will be one of the most important papers in cardiovascular medicine in years,” said Charles Murry, a heart researcher at the University of Washington in Seattle. “It helps settle a longstanding controversy about whether the human heart has any ability to regenerate itself.”

If the heart can generate new muscle cells, researchers can hope to develop drugs that might accelerate the process, since the heart fails to replace cells that are killed in a heart attack.

The dogma that the heart cannot generate new muscle cells has been challenged since 1987 by a somewhat lonely skeptic, Piero Anversa, now of the Harvard Medical School. Anversa maintains that heart muscle cells are renewed so fast that a person dying at age 80 has replaced the heart four times over. Many other researchers have doubted this assertion.

Cell turnover rates can easily be measured in animals by making their cells radioactive and seeing how fast they are replaced. Such an experiment, called pulse-labeling, could not ethically be done in people.

But Frisen realized several years ago that nuclear weapons tested in the atmosphere until 1963 had in fact labeled the cells of the entire world’s population.

The nuclear blasts generated a radioactive form of carbon, known as carbon-14. The amount of carbon-14 in the atmosphere has gradually diminished since 1963, when above-ground tests were banned, because it has been incorporated into plants and animals or diffused into the oceans.

In the body, carbon-14 in the diet gets into the DNA of new cells and stays unchanged for the life of the cell.

Because the level of carbon-14 in the atmosphere falls each year, the amount of carbon-14 in the DNA can serve to indicate the cell’s birthdate, Frisen found.

Four years ago he used his new method to assess the turnover rate of various tissues in the body, concluding that the average age of the cells in an adult’s body might be as young as seven to 10 years. But there is a wide range of ages — from the rapidly replaced cells of the blood and gut to the mostly permanent cells of the brain.

Frisen has successfully applied his method to the heart muscle cells, but had to navigate a series of technical obstacles created by the special behavior of the cells. Many have two nuclei, instead of the usual one, and within these double nuclei the DNA may be duplicated again.

“I was really impressed at the level of rigor they put into this analysis,” Murry said, calling it a “scientific tour de force.”